Mechanical Engineering Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, 15213, Pennsylvania, United States of America.
Biomedical Engineering Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, 15213, Pennsylvania, United States of America.
Neuroinformatics. 2023 Jan;21(1):163-176. doi: 10.1007/s12021-022-09600-8. Epub 2022 Sep 7.
Neuron morphology gives rise to distinct axons and dendrites and plays an essential role in neuronal functionality and circuit dynamics. In rat hippocampal neurons, morphological development occurs over roughly one week in vitro. This development has been qualitatively described as occurring in 5 stages. Still, there is a need to quantify cell growth to monitor cell culture health, understand cell responses to sensory cues, and compare experimental results and computational growth model predictions. To address this need, embryonic rat hippocampal neurons were observed in vitro over six days, and their processes were quantified using both standard morphometrics (degree, number of neurites, total length, and tortuosity) and new metrics (distance between change points, relative turning angle, and the number of change points) based on the Change-Point Test to track changes in path trajectories. Of the standard morphometrics, the total length of neurites per cell and the number of endpoints were significantly different between 0.5, 1.5, and 4 days in vitro, which are typically associated with Stages 2-4. Using the Change-Point Test, the number of change points and the average distance between change points per cell were also significantly different between those key time points. This work highlights key quantitative characteristics, both among common and novel morphometrics, that can describe neuron development in vitro and provides a foundation for analyzing directional changes in neurite growth for future studies.
神经元形态决定了轴突和树突的独特性，在神经元功能和电路动力学中起着至关重要的作用。在大鼠海马神经元中，形态发生大约在体外进行一周。这种发育已经被定性地描述为经历了 5 个阶段。尽管如此，仍需要量化细胞生长情况以监测细胞培养的健康状况，了解细胞对感觉线索的反应，并比较实验结果和计算生长模型的预测。为了满足这一需求，在体外观察了胚胎大鼠海马神经元 6 天，并使用基于变化点检验的标准形态计量学（角度、神经突数量、总长度和扭曲度）和新的度量标准（变化点之间的距离、相对转角和变化点的数量）来量化它们的过程，以跟踪轨迹的变化。在标准形态计量学中，细胞内神经突的总长度和端点数量在体外 0.5、1.5 和 4 天之间存在显著差异，这通常与第 2-4 阶段相对应。使用变化点检验，每个细胞的变化点数量和平均变化点之间的距离在这些关键时间点之间也存在显著差异。这项工作突出了关键的定量特征，包括常见和新颖形态计量学中的特征，这些特征可以描述体外神经元的发育，并为未来研究中神经突生长的方向变化分析提供了基础。
